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梭状回亚区功能连接的分子基础:转录组-神经影像学空间相关性研究。

Molecular basis underlying functional connectivity of fusiform gyrus subregions: A transcriptome-neuroimaging spatial correlation study.

机构信息

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei, China; Anhui Provincial Institute of Translational Medicine, Hefei, China.

Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China; Research Center of Clinical Medical Imaging, Anhui Province, Hefei, China; Anhui Provincial Institute of Translational Medicine, Hefei, China.

出版信息

Cortex. 2022 Jul;152:59-73. doi: 10.1016/j.cortex.2022.03.016. Epub 2022 Apr 13.

DOI:10.1016/j.cortex.2022.03.016
PMID:35526385
Abstract

The fusiform gyrus (FG) subserves a range of visual cognitive functions likely arising from its distinct subregions that present different connectivity profiles. Nevertheless, the molecular basis underlying such connectivity variability across FG subregions is still an open question. Resting-state functional magnetic resonance imaging (fMRI) data were collected from a discovery dataset (361 healthy subjects) and two independent cross-race, cross-scanner validation datasets (103 and 329 healthy subjects). We adopted a newly developed standardized pipeline to process gene expression data from the Allen Human Brain Atlas. Fine-grained FG subregions derived from the Human Brainnetome Atlas were utilized to measure seed-based resting-state functional connectivity (rsFC). Then, transcriptome-neuroimaging spatial association analyses were conducted to identify genes related to rsFC of each FG subregion. Results showed that rsFC of the left A37mv was associated with expression measures of 1063 genes, while there were no expression-rsFC correlations for the other subregions. The 1063 genes were mainly enriched for biological functions and pathways related to synaptic transmission, neurons, and neurotransmitter systems as well as for autism spectrum disorder. Specific expression analyses revealed that these rsFC-related genes were specifically expressed in brain tissue, in cortical neurons and immune cells, and during nearly all developmental periods. In addition, these genes were associated with multiple behavioral domains such as vision, language, and sensation. Finally, protein-protein interaction (PPI) analysis demonstrated that the genes could construct a PPI network with 37 hub genes. These findings may offer unique insights into the molecular basis underlying the functional heterogeneity of the FG.

摘要

梭状回(FG)支持一系列视觉认知功能,可能源于其不同的亚区具有不同的连接模式。然而,FG 亚区之间连接变异性的分子基础仍然是一个悬而未决的问题。从发现数据集(361 名健康受试者)和两个独立的跨种族、跨扫描仪验证数据集(103 名和 329 名健康受试者)中收集了静息状态功能磁共振成像(fMRI)数据。我们采用了一种新开发的标准化流程来处理来自艾伦人类大脑图谱的基因表达数据。利用人类脑连接图谱中精细的 FG 亚区来测量基于种子的静息状态功能连接(rsFC)。然后,进行转录组-神经影像学空间关联分析,以确定与每个 FG 亚区 rsFC 相关的基因。结果表明,左 A37mv 的 rsFC 与 1063 个基因的表达测量值相关,而其他亚区则没有表达-rsFC 相关性。这 1063 个基因主要富集在与突触传递、神经元和神经递质系统以及自闭症谱系障碍相关的生物学功能和途径中。特异性表达分析表明,这些 rsFC 相关基因特异性地在脑组织、皮质神经元和免疫细胞中表达,并在几乎所有发育阶段表达。此外,这些基因与视觉、语言和感觉等多个行为领域相关。最后,蛋白质-蛋白质相互作用(PPI)分析表明,这些基因可以构建一个包含 37 个枢纽基因的 PPI 网络。这些发现可能为 FG 功能异质性的分子基础提供独特的见解。

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